PROJECT SUMMARY ? PROJECT 2 Prior research has demonstrated that health care provider recommendation is the most influential factor affecting HPV vaccine uptake and completion among adolescents and young adults. However, many providers are not recommending the vaccine at opportunistic times such as the targeted ages of 11-12 when most children receive Tdap and meningococcal vaccines. To improve the uptake of the HPV vaccine among 11-12 year olds ? the age group of focus for the Centers for Disease Control and Prevention (CDC) ? a multi-disciplinary research team across four Appalachian states will test the effectiveness of a health system-based intervention, as part of an integrated clinic-based cervical cancer prevention program (with Projects 1 and 3), that is directed to three levels of influence ? clinic, provider, and patient. Using a delayed intervention design in a group randomized implementation trial, we will examine outcomes of effectiveness, acceptability, and sustainability along the Implementation Science Framework. We will also test in a secondary aim whether interventions targeted to the 13-26 year olds increases catch-up vaccination. This study is part of the Program Project, ?Improving Uptake of Cervical Cancer Prevention Services in Appalachia,? and as such, is intricately integrated with the Cores of the Program. The interventions to be tested have been developed in conjunction with community partners, address multi-level factors within the Social Determinants of Health that impact disparities in HPV-related disease, and have been piloted in Appalachian populations. Specific aims are to: 1) Primary Outcome: Test the effectiveness of a multi-level intervention directed at clinics, providers, and patients (parents of children aged 11-12) to improve HPV vaccine initiation and completion in health systems in four Appalachian states (KY, OH, WV, and VA) among children aged 11-12, and assess the effectiveness of the intervention program among subgroups, e.g., females vs males; 2) Secondary Outcomes: Assess: a) sustainability of the intervention; b) cost impacts of the intervention; c) changes in clinic practices that occur as a result of the intervention in terms of staff responsibilities for the vaccination process and reducing missed opportunities for vaccination; and d) whether interventions directed to 13-26 year olds increases catch-up vaccination; and 3) Secondary Outcomes: Examine: a) changes in knowledge and attitudes of providers via educational session pre-post surveys and b) satisfaction with the intervention at the multiple levels. If effective, this multi-level intervention will be disseminated to our clinical and community partners as well as other partners throughout Appalachia to facilitate the uptake of effective interventions throughout health systems and clinics in Appalachia to help reduce the burden of HPV-preventable diseases.